Estimating the proportion of true null hypotheses and adaptive false discovery rate control in discrete paradigm.

Storey's estimator for the proportion of true null hypotheses, originally proposed under the continuous framework, has been modified in this work under the discrete framework. The modification results in improved estimation of the parameter of interest. The proposed estimator is used to formulate an adaptive version of the Benjamini-Hochberg procedure.

Biophysical Correlates of Enhanced Immunogenicity of a Stabilized Variant of the Receptor Binding Domain of SARS-CoV-2.

The receptor binding domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We have previously reported the design and characterization of a mammalian cell expressed RBD derivative, mRBD1-3.2, that has higher thermal stability and greatly enhanced immunogenicity relative to the wild type mRBD.

Structural and Functional Characterization of Rv0792c from Mycobacterium tuberculosis: Identifying Small Molecule Inhibitor against HutC Protein.

In order to adapt in host tissues, microbial pathogens regulate their gene expression through a variety of transcription factors. Here, we have functionally characterized Rv0792c, a HutC homolog from Mycobacterium tuberculosis. In comparison to the parental strain, a strain of M.

Ter-Seq: A high-throughput method to stabilize transient ternary complexes and measure associated kinetics.

Regulation of biological processes by proteins often involves the formation of transient, multimeric complexes whose characterization is mechanistically important but challenging. The bacterial toxin CcdB binds and poisons DNA Gyrase. The corresponding antitoxin CcdA extracts CcdB from its complex with Gyrase through the formation of a transient ternary complex, thus rejuvenating Gyrase.

Combining cysteine scanning with chemical labeling to map protein-protein interactions and infer bound structure in an intrinsically disordered region.

The genome harbours nine toxin-antitoxin (TA) systems of the mazEF family. These consist of two proteins, a toxin and an antitoxin, encoded in an operon. While the toxin has a conserved fold, the antitoxins are structurally diverse and the toxin binding region is typically intrinsically disordered before binding.

Mechanistic insights into global suppressors of protein folding defects.

Most amino acid substitutions in a protein either lead to partial loss-of-function or are near neutral. Several studies have shown the existence of second-site mutations that can rescue defects caused by diverse loss-of-function mutations. Such global suppressor mutations are key drivers of protein evolution.

Functional and Biochemical Characterization of the MazEF6 Toxin-Antitoxin System of Mycobacterium tuberculosis.

The Mycobacterium tuberculosis genome harbors nine toxin-antitoxin (TA) systems that are members of the family, unlike other prokaryotes, which have only one or two. Although the overall tertiary folds of MazF toxins are predicted to be similar, it is unclear how they recognize structurally different RNAs and antitoxins with divergent sequence specificity. Here, we have expressed and purified the individual components and complex of the MazEF6 TA system from M.

Identification of stabilizing point mutations through mutagenesis of destabilized protein libraries.

Although there have been recent transformative advances in the area of protein structure prediction, prediction of point mutations that improve protein stability remains challenging. It is possible to construct and screen large mutant libraries for improved activity or ligand binding. However, reliable screens for mutants that improve protein stability do not yet exist, especially for proteins that are well folded and relatively stable.

Rapid Identification of Secondary Structure and Binding Site Residues in an Intrinsically Disordered Protein Segment.

harbours nine toxin-antitoxin (TA) systems of the MazEF family. MazEF TA modules are of immense importance due to the perceived role of the MazF toxin in persistence and disease. The MazE antitoxin has a disordered C-terminal domain that binds the toxin, MazF and neutralizes its endoribonuclease activity.

Bias-corrected estimators for proportion of true null hypotheses: application of adaptive FDR-controlling in segmented failure data.

Two recently introduced model-based bias-corrected estimators for proportion of true null hypotheses ( ) under multiple hypotheses testing scenario have been restructured for random observations under a suitable failure model, available for each of the common hypotheses. Based on stochastic ordering, a new motivation behind formulation of some related estimators for is given. The reduction of bias for the model-based estimators are theoretically justified and algorithms for computing the estimators are also presented.

VapC21 Toxin Contributes to Drug-Tolerance and Interacts With Non-cognate VapB32 Antitoxin in .

The prokaryotic ubiquitous Toxin-antitoxin (TA) modules encodes for a stable toxin and an unstable antitoxin. VapBC subfamily is the most abundant Type II TA system in genome. However, the exact physiological role for most of these Type II TA systems are still unknown.

Mechanism of CcdA-Mediated Rejuvenation of DNA Gyrase.

Most biological processes involve formation of transient complexes where binding of a ligand allosterically modulates function. The ccd toxin-antitoxin system is involved in plasmid maintenance and bacterial persistence. The CcdA antitoxin accelerates dissociation of CcdB from its complex with DNA gyrase, binds and neutralizes CcdB, but the mechanistic details are unclear.

Facile measurement of protein stability and folding kinetics using a nano differential scanning fluorimeter.

With advancements in high-throughput generation of phenotypic data on mutant proteins, it has become important to individually characterize different proteins or their variants rapidly and with minimal sample consumption. We have made use of a nano differential scanning fluorimetric device, from NanoTemper technologies, to rapidly carry out isothermal chemical denaturation and measure folding/unfolding kinetics of proteins and compared these to corresponding data obtained from conventional spectrofluorimetry. We show that using sample volumes 10-50-fold lower than with conventional fluorimetric techniques, one can rapidly and accurately measure thermodynamic and kinetic stability, as well as folding/unfolding kinetics.

1.6:1 bandwidth two-layer antireflection structure for silicon matched to the 190-310 GHz atmospheric window.

Although high-resistivity, low-loss silicon is an excellent material for terahertz transmission optics, its high refractive index necessitates an antireflection treatment. We fabricated a wide-bandwidth, two-layer antireflection treatment by cutting subwavelength structures into the silicon surface using multi-depth deep reactive-ion etching (DRIE). A wafer with this treatment on both sides has <-20  dB (<1%) reflectance over 187-317 GHz at a 15° angle of incidence in TE polarization.

Two-stage test of means of unordered pairs.

The problem of testing equality of means of a bivariate normal distribution on the basis of a sample of size n has been considered when the labels of the observations are either missing or not known. The problem may arise in many applied settings, especially in genetics. Classical likelihood ratio test fails here because of identifiability problems.

Falciform ligament flap for the protection of the gastroduodenal artery stump after pancreaticoduodenectomy: A single center experience.

Aim Of The Study: Delayed hemorrhage, though rare, remains a significant source of morbidity and mortality after pancreaticoduodenectomy (PD). An important cause of this delayed hemorrhage is erosion or pseudoaneurysm formation of the gastroduodenal artery (GDA) by pancreatic enzymes and adjacent intra-abdominal sepsis. So protection of the GDA stump may avoid this devastating complication.

Frey procedure for chronic pancreatitis in children: A single center experience.

Background: There is paucity of literature regarding the Frey procedure for children with chronic pancreatitis. The purpose of this study is to present our experience with the Frey procedure in children.

Methods: This is an observational retrospective review study.

On-chip lectin microarray for glycoprofiling of different gastritis types and gastric cancer.

An on-chip lectin microarray based glycomic approach is employed to identify glyco markers for different gastritis and gastric cancer. Changes in protein glycosylation have impact on biological function and carcinogenesis. These altered glycosylation patterns in serum proteins and membrane proteins of tumor cells can be unique markers of cancer progression and hence have been exploited to diagnose various stages of cancer through lectin microarray technology.

Simultaneous identification of growth law and estimation of its rate parameter for biological growth data: a new approach.

Scientific formalizations of the notion of growth and measurement of the rate of growth in living organisms are age-old problems. The most frequently used metric, "Average Relative Growth Rate" is invariant under the choice of the underlying growth model. Theoretically, the estimated rate parameter and relative growth rate remain constant for all mutually exclusive and exhaustive time intervals if the underlying law is exponential but not for other common growth laws (e.

Malrotation of Intestine with Carcinoma Colon in Adult.

Malrotation of gut is a congenital anomaly and patients usually present in childhood. Occasionally it may present in adulthood. Patients are usually asymptomatic when malrotation of gut is detected during investigations or operation.

Antigen-specific induced T regulatory cells impair dendritic cell function via an IL-10/MARCH1-dependent mechanism.

Foxp3(+) T regulatory cells (Tregs) are critically important for the maintenance of immunological tolerance, immune homeostasis, and prevention of autoimmunity. Dendritic cells (DCs) are one of the major targets of Treg-mediated suppression. Some studies have suggested that Treg-mediated suppression of DC function is mediated by the interaction of CTLA-4 on Tregs with CD80/CD86 on the DCs resulting in downregulation of CD80/CD86 expression and a decrease in costimulation.